Our objective is to determine the role of locally produced prostaglandins in regulation of the circulation. This proposal will focus on the renal, gastrointestinal, adrenal and uteroplacental circulations. There are data available that indicate a potential role for prostaglandins in each of these organ systems. Our approach will be to use electromagnetic flowmeters and radioactive microspheres to determine changes in regional blood flow and gas chromatography-mass spectrometry and/or radioimmunoassay for measurement of prostaglandins and metabolites in body fluids. In the kidney we will determine the potential role of prostacyclin (PGI2) in producing vascular effects and release of renin. The renin releasing mechanism affected by the prostaglandin system will be investigated in detail. The possibility that prostaglandin-induced circulatory changes modulate the response to vasopressin will be investigated. We will also study the role of prostaglandins in protecting the gastrointestinal circulation from the vasoconstriction effects of cardiac glycosides and other drugs and hormones. The possibility that prostaglandins are responsible for the circulatory effects of furosemide will be determined. Specifically, we are interested in the potential for furosemide-induced prostaglandin release to decrease blood flow to the pregnant uterus and placenta. The adrenal vascular response to ACTH, and the participation of locally produced prostaglandins on this response will be studied. Finally, we wish to investigate the hemodynamic responses of the rat to exogenous and endogenously produced prostaglandins to determine whether studies of prostaglandins in the rat are relevant to other species. Our studies will provide information on the circumstances where prostaglandins are important regulators of regional blood flow. Additionally, these experiments may provide mechanisms for some of the adverse effects of drugs that inhibit or stimulate prostaglandin synthesis and may also discover potentially important interactions between vasoactive drugs and prostaglandin synthesis inhibitors.